The proposed research will (1) characterize the action of volatile anesthetics (halothane and enflurane) on the cyclic 3',5'-adenosine monophosphate (cAMP) system of myocardium, (2) define the role of cAMP in the cardiac effect of anesthetic and (3) identify the sites of action, mechanism of action and the pharmacological effects of these anesthetics which are mediated by cAMP in heart. To achieve these goals, changes in enzyme activity, cAMP content, receptor characteristics caused by anesthetics and anesthetic adjuvant drugs as well as their interaction with transmitters and modulators controlling cardiac function will be determined. This study will establish whether, in fact, there is an association between the effects of these anesthetics on the heart (cardiac-depression and the sensitization of the conductive system of the heart to catecholamines) and the cAMP system in the heart. Canine cardiac Purkinje fibers and ventricular muscle will be used for in vitro biochemical and functional studies. The effects of halothane, at increasing concentrations, on adenylate cyclase will be determined in tissue homogenates by the method of Krishna. cAMP content in intact tissue will be measured according to Gilman. The effect of anesthetics on receptor characteristics in a membrane preparation will be determined according to Alexander et al. Protein content will be measured by the procedure of Lowry.